nephrology unit mansoura faculty of medicine - مصر · pathology of nephrotic syndrome ......
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Nephrotic Syndrome
A syndrome characterized by:
1. Heavy proteinuria (> 3.5 gm/1.73 m2/d.)
2. Massive oedema.
3. Hypoalbminaemia.
4. Hyperlipidaemia.
Causes
1ry glomerular disease (no identifiable cause)
2ry NS due to any of the following:
– Infection or post infection (Schistosoma, Malaria, HCV,HBV,…etc.)
– Drugs: gold, penicillamin, NSAIDs, …etc.
– Metabolic: diabetes mellitus, amyloidosis, …etc.
– Collagen & Autoimmune disease: SLE, Vasculitis, …etc.
– Malignancy: Lymphoma, Multiple Myeloma, …etc.
– Congenital and familial conditions
Pathology of Nephrotic Syndrome
• Minimal change nephritis.
• Focal and segmental glomerulosclerosis.
• Membranous glomerulonephritis.
• Proliferative glomerulonephritis.
• Mesangial proliferative.
• Mesngiocapillary.
• Crescentic GN.
• IgA nephropathy.
Hypoalbuminaemia
1. Albuminuria
2. The decreased intake (due to anorexia)and decreased absorption(due to oedemaof the intestinal wall).
3. The increased concentration of albumin inthe glomerular filtrate which isaccompanied by increase in its catabolismby the renal tubules.
4. Sometimes decreased rate of hepaticbiosynthesis of albumin.
Glomerular damage
Proteinuria
Hypoalbuminaemia
Decreased plasma oncotic pressure
Water
retention OedemaWater
retention
• increasedangiotensin,aldosterone
•Decreased ANP
Decreased effective circulating blood volume
Pathogenesis of Oedema
in N. S.
Increase Increased ADH
oedema
Hyperlipidemia in N. S.
• ↑ Cholesterol, VLDL, LDL
• ↑triglycerids, ↓ HDL
– ↑ Hepatic synthesis
– ↓Catabolism due to inhibition of lipoptn lipase.
Oedema
Soft pitting
Swelling of the face in the morning &
ankles in the evening
Later it become persistent and there may
be generalized anasarca
Manifestations of fluid retention
Mental dullness, headache,convulsions.
Lassitude, anorexia,malabsorption.
Wt gain.
Increase JVP, pul crepitations.
Complications of N. S.Infection
•Especially upper respiratory, urinary, skin andperitoneal infections.
•Recurrent infection is due to nutritionaldeficiencies, urinary loss of immunoglobulins.
Complications of N. S.Clotting episodes
•These manifest as arecurrent DVT, orrenal vein thrombosis.
• It may becomplicated bypulmonary embolism.
Clotting episodes
causes
1. Increased concentration of coagulationfactors resulting from an increased hepaticsynthesis e.g. fibrinogen, factor III, and VIII.
2. Urinary loss of antithrombin III and protein Cwhich normally act against intravascularclotting.
3. Abnormal vascular endothelium.
4. Hypovolemic state
Complications of N. S.Premature atherosclerosis
•it is due to hyperlipidaemia
•This complication occurs mainly in cases withfrequent relapses or cases resistant to treatment
HypovolaemiaWhich causes postural hypotension.
Complications of N. S.
Hypertension
• In nearly 50% of the cases, according to the etiologic and pathologic type of NS
– Idiopathic minimal change NS cases are always normotensive while cases with mesangiocapillary GN whether idiopathic or secondary are always hypertensive.
• Corticosteroid ttt & pts developing CKD may be the cause of HTN
Complications of N. S.
Acute renal failure
• this may be due to severe hypovolaemia (dueto the severe hypoalbuminaemia and use ofbig doses of diuretics), or due to acuteinterstitial nephritis (drug induced as largedose of furosemide).
Complications of N. S.
Bone disease
• Due to hypocalcemia (resulting from deficientintake and urinary loss of vitamin D bindingglobulin). It causes secondaryhyperparathyroidism.
Anaemia
• Due to nutritional deficiencies and urinary lossof transferrin.
Complications of N. S.
Drug related complications:
1. Diuretics which may cause hypovolaemia,hypokalaemia, or hyponatraemia.
2. Corticosteroids that may cause diabetesmellitus, cataract, D.U., infections, and bonedisease.
3. Other Immunosuppressive drugs ascyclophosphamide which may causehaemorrhagic cystitis, alopecia, infection andmalignancy.
Laboratory Investigation
Urinalysis : RBCs, RBCs cast,proteinuria.
Quantitative urinary protein. Nephroticrange proteinuria (>3.5 gm/24h),subnephrotic range.
Renal function tests: blood urea,creatinine, estimated GFR, creatinineclearance.
Kidney biopsy
Renal biopsy is generally required to establish
the type of glomerular disease and to guide
treatment decisions
Investigation to diagnose the underlying
causes:
• ANA (antinuclear antidoy) Anti-ds DNA positive insystemic lupus erythromatosis (SLE).
• C3, C4 (complement) may be consumed.
• ASOT (anti-streptolysin O titre) positive in poststreptococcal GN.
• ANCA (antineutrophilic antibody) positive in Wagnergranulomatosis.
• Antiglomerular basement membrane (AGBM) positivein Goodpasuture syndrome
Treatment of N. S.
Treatment of the cause in secondary
cases- for example- by proper control of
blood sugar in D.M. and steroids and
immunosuppressive drugs in SLE.
Treatment of complications as infection
by antibiotics
Treatment of N. S.
Diet
Salt restricted supported with vitamins
especially vitamin D and calcium.
Protein content should equal the daily
physiologic needs (1g/kg) plus the amount
of daily urinary protein loss
e.g. a 60kg patient who loses 10 gm daily
should be given 70 gm protein containing diet.
Treatment of N. S.
Diuretics
Mainly loop diuretics (e.g. Frusemide)initially can be given orally in variabledoses (according to severity and responsee.g. 20-60 mg/d.).
In severe resistant cases doses up to 120mg. I.V. may be given.
Addition of metolazone (a thiazidediuretic) may have a potentiating effectfor frusemide in diuretic resistant cases.
Treatment of N. S.
Salt poor albumin
is expensive and when given is lost
quickly in urine.
So it is indicated only when there is
◦ severe oedema resistant to large doses of
diuretics
◦ and if the nephrotic patient is to be subjected
to surgery or invasive procedure (e.g. biopsy)..
Treatment of N. S.
Hypertension
Blood pressure control is important for bothrenal and cardiovascular protection.
For patients with proteinuria of more than 1g/day, the target for blood pressure is 125/75mm Hg unless contraindicated for clinicalreasons
ACEI and ARBs are cardioprotective andcan reduce proteinuria and slow progressionof renal disease in both diabetic andnondiabetic patients with chronicnephropathy
Treatment of N. S.
Corticosteroids
are given when there is no response to
previous lines of treatment.
Minimal change glomerulonephritis gives
the best response while mesangiocapillary
glomerulonephritis is always steroid
resistant.
Corticosteroids
For patients with secondary GN, steroids
are given if indicated for the causative
disease as in SLE but not in D.M.
The dose and duration of steroid treatment
depends on the type of disease and
response.
Corticosteroids
In primary (idiopathic) minimal change
Prednisolone is given orally in a dose of 60 mg / day
(max. 80mg/d) .
This full dose is to be given for 8-12 weeks then
tapered gradually over equal time period.
In severe cases 1-3 doses of Methylprednisolone is
given by I.V. infusion ( 10-15mg/kg) as induction,
followed by oral prednisolone.
Immunosuppressive drug
Cyclosporin is an immunosuppresive drug
which is commonly added to steroids(e.g.
steroid resistant and steroid dependant
cases ), and in patients with membranous
nephropathy.
Other commonly used immunosuppresive
drugs includes
Azathioprine,Cyclophosphamide,and
MMF(Cell Cept).
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